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Clinical Trial
. 2024 Aug 9;15(1):6822.
doi: 10.1038/s41467-024-51264-2.

Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial

Romain Guièze  1   2 , Loïc Ysebaert  3 , Damien Roos-Weil  4 , Luc-Mathieu Fornecker  5 , Emmanuelle Ferrant  6 , Lysiane Molina  7 , Thérèse Aurran  8 , Aline Clavert  9 , Sophie de Guibert  10 , Anne-Sophie Michallet  11 , Alain Saad  12 , Bernard Drénou  13 , Philippe Quittet  14 , Bénédicte Hivert  15 , Kamel Laribi  16 , Julie Gay  17 , Anne Quinquenel  18 , Julien Broseus  19   20 , Valérie Rouille  21 , David Schwartz  21 , Benoit Magnin  22 , Grégory Lazarian  23 , Lauren Véronèse  24   25 , Marie de Antonio  26 , Camille Laurent  27 , Olivier Tournilhac  28   24 , Bruno Pereira  26 , Pierre Feugier  20   29
Affiliations
Clinical Trial

Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial

Romain Guièze et al. Nat Commun. .

Abstract

Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 μg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.

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Conflict of interest statement

R.G. reports research grants from Amgen, AstraZeneca, Roche, Janssen, Abbvie, and BeiGene; consulting fees; honoraria; and travel funds from AstraZeneca, Roche, Janssen, Abbvie, and BeiGene. J.G. reports consulting fees, honoraria, and travel funds from AstraZeneca, Janssen, Sanofi. E.F. reports consulting fees, honoraria, and travel funds from AstraZeneca, Janssen, Abbvie, and BeiGene. A.C. reports consulting fees, honoraria and travel funds from AstraZeneca, Roche, Janssen, and Abbvie. J.B. reports honoraria from AstraZeneca and Janssen, and travel funds from AstraZeneca and Abbvie. K.L. has received research grants from AbbVie, AstraZeneca, Novartis, BeiGene, Amgen, as well as personal fees from AbbVie, Novartis, BMS, BeiGene, Takeda, Janssen, AstraZeneca, and Amgen. P.F. reports, consulting fees, honoraria, and travel funds from AstraZeneca, Roche, Gilead, Janssen, BeiGene, and Lilly. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Trial profile with patient disposition.
R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
Fig. 2
Fig. 2. Characteristics of response and progression during the study for the 25 patients treated with blinatumomab.
R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Duration of response (a) in the 9 patients responding to blinatumomab induction; progression-free survival (b), and overall survival (c) in the 25 blinatumomab-treated patients.
Related Kaplan-Meier curves are denoted by red lines, with plots representing censored data. Dashed grey lines indicate 95% confidence intervals. Source data are provided as a Source Data file.
See this image and copyright information in PMC

References

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